摘要:

Strong genetic evidence supports the idea that point mutations in the promoter ofγ-globin genes overexpressed in adult age [hereditary persistence of fetal hemoglobin (HPFH)] are responsible for the observed phenotype. DNA binding sites for ubiquitous and/or erythroid specific nuclear proteins correlate in location with the positions of point mutations responsible for HPFH. The analysis of the effects of one of these mutations (−175 T°C) onin vitrobinding of nuclear proteins and on the activity of the mutated promoter in transfection assays indicates that altered binding of the erythroid-specific protein NFE-1 may be responsible for increased activity of the mutated promoter. Other HPFH mutations close to the distal CCAAT box (−117 G→A and 13 nucleotide deletions, -114 to -102) have complex effects onin vitrobinding of nuclear proteins; their only common effect is the loss of binding of the erythroid-specific factor NFE3. If mechanisms generating the HPFH phenotype are homogeneous, NFE3 might be a negatively acting factor; alternatively, heterogeneous mechanisms might operate and HPFH might additionally be related to loss of binding to the distal CCAAT box region of either NFE1 (−117 HPFH) or of the ubiquitous CCAAT displacement protein-CDP (13 nucleotides deletion).

ISSN:0363-0269    

DOI:10.3109/03630268908993104

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Three different hemoglobinopathies, i.e. Hb S, Hb Chad [α23 (B4)Glu→Lys], andα-thalassemia-2 (−3.7) have been observed in eight members of a family from Surinam. The proposita had all three abnormalities, while her mother and four of her half-brothers had Hb Chad together with anα-thalassemia-2 heterozygosity or homozygosity. Gene mapping and dot-blot analysis of amplified DNA identified a G→A mutation in codon 23 of theα2αl hybrid gene resulting in the Glu→Lys substitution. The quantity of theα-Chad chain averaged 31.5% in its carriers with an additionalα-thalassemia-2 heterozygosity [-αCnad(−3.7 kb)/αα], and 43% in the two carriers with an additionalα-thalassemia-2 homozygosity [-αChad(−3.7 kb)/-α(3.7 kb)]. These quantities are considerably higher than those reported for families from Chad, China, and Japan; the low levels of 14.5-24% Hb Chad in members of previously reported cases suggest a mutation on a chromosome with twoα-globin genes [ααChad/ααorαChadα/αα].

ISSN:0363-0269    

DOI:10.3109/03630268908993105

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Structural analysis o f theαchain of the hemoglobin from a Caucasian female with a mild hemolytic anemia showed the presence of a variant with a Val→Met substitution at positionα62. The valine at this position forms one o f the contacts with heme and its replacement by methionine will likely decrease heme binding and cause adistortion of the heme crevice and a decreased stability of the abnormal protein. Dot-blot analysis of amplified DNA with32P-labeled synthetic oligonucleotide probes confirmed the suspected G→A mutation in the first position of codon 62, and also located the mutation in theα2-globin gene. The mutation was found in the proposita and one of her daughters but was most probably absent in her parents.

ISSN:0363-0269    

DOI:10.3109/03630268908993106

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Oxygen equilibrium studies of purified Hb Camperdown [βl04(G6)Arg→Ser] have revealed an increased oxygen affinity at acid pH, while it is decreased for pH values above 7.4. This accounts for an almost 40% reduction in the alkaline Bohr effect. The effects of chloride and organophosphate effectors on the oxygen affinity of Hb Camperdown are inhibited by 40-50%. in chloridefree Hepes buffer, Hb Camperdown exhibits a lower oxygen affinity than normal Hb A. The present results confirm the important role of the positively charged residues lining theβ1β2interface in regulating the functional properties of hemoglobin.

ISSN:0363-0269    

DOI:10.3109/03630268908993107

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Hb G-San Jose [α2β27(A4)Glu→Gly] was detected in four families and three unrelated individuals from Eastern Sicily. Polymorphic restriction sites within theβ-globin gene cluster bearing the mutation were characterized. A complete association ofβ-G-San Jose alleles with Mediterranean haplotype IV was found in the families examined and the same haplotype was also present in the unrelated individuals. These findings support the hypothesis of an unicentric origin of theβ-G-San Jose mutation which may have arisen in Eastern Sicily.

ISSN:0363-0269    

DOI:10.3109/03630268908993108

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

β-Thalassemia is a common disease in Southern China and 10 different mutations or frameshifts are responsible for most types ofβ-thalassemia in this area. We studied 126 chromosomes of 80β-thalassemia patients from the Guangxi, Guangdong, and Sichuan Provinces using the polymerase chain reaction followed by dot-blot hybridization with specific oligonucleotide probes. The most common mutation in the three provinces is the frameshift at codons 41-42, followed by the A→T mutation at codon 17. The A→G mutation at nt -29 of the promoter is common in Sichuan but not in the other two provinces. Three mutations (T→C at nt -30; G→T at IVS-I-1, and G→C at IVS-I-5) were not observed. These data were used to initiate a prenatal diagnosis program using the same techniques for identification. Eleven fetuses at risk forβ-thalassemia have been diagnosed.

ISSN:0363-0269    

DOI:10.3109/03630268908993109

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

Sequence analysis and dot-blot hybridization of DNA from a Greek patient with a transfusion dependent thalassemia revealed the combination of aβIVS-I-1 G→-A mutation (β˚-thalassemia) and a hitherto undescribed frameshift mutation; the latter concerns the absence of a CT dinucleotide from codon 5 and results in a termination signal at the new codon 21 (also aβ˚-thalassemia).

ISSN:0363-0269    

DOI:10.3109/03630268908993110

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

摘要:

A variety of regimens were utilized on KMOE cells to maximally raise globin mRNA levels for the purpose of improving the usefullness of this line for globin gene studies. Steady-state mRNA levels of embryonic (ϵ), fetal (γ) and adult (β) globin genes were assayed by the S1-nuclease protection method before and after exposure to inducing compounds. Exposure of KMOE cells to cytosine arabinoside and hemin leads to over 20-fold increases inβ- andγ-globin mRNA steady-state levels, and an over 60-fold increase inϵ-globin mRNA level. Exposure to cytosine arabinoside alone inducedβ- andϵ-globin but notγ-globin gene expression. Theα-like globin genes (ζandα) were also monitored but found to be poorly expressed and not significantly inducible. The presence ofϵ-globin mRNA and the lack ofα-globin mRNA distinguishes this line, KMOE-EL, from the KMOE sublines previously described.

ISSN:0363-0269    

DOI:10.3109/03630268908993111

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630268908993112

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630268908993113

出版商:Taylor&Francis    

年代:1989

数据来源: Taylor